NEUTROPHIL MIGRATION INTO THE PERITONEUM IS P-SELECTIN DEPENDENT, BUTSEQUESTRATION IN LUNGS IS SELECTIN INDEPENDENT DURING PERITONITIS

Neutrophil (PMN) influx into the peritoneal cavity in response to bact erial peritonitis is an indispensable aspect of host defense. PMNs als o are responsible for the remote organ injury observed after major abd ominal infection. The aim of this study was to examine the effect of s electin blockade on PMN migration into the peritoneum and on PMN seque stration in the lungs, early in the course of peritonitis. Cecal ligat ion and puncture (CLP) was performed on P-selectin-deficient (P-def) m ice and their genetic controls (C57). Both groups were treated with an ti-E-selectin antibody, anti-L-selectin, or isotypic control immunoglo bulin G at the time of CLP. 6 h after CLP, mice were sacrificed. Perit oneal PMN migration decreased in P-def mice compared with C57 controls after CLP. Blockade of E- or L-selectin alone in controls did not alt er peritoneal PMN influx or circulating PMNs after CLP. In the P-def m ice, treatment with anti-E-antibody or anti-L-antibody nearly eliminat ed PMN influx into the peritoneum. In contrast, circulating PMNs marke dly increased after CLP in P-def mice when compared with baseline valu es. Lung myeloperoxidase increased in all groups of mice following CLP , Blockade of P-selectin with anti-P-selectin antibody elicited a resp onse similar to that observed in the P-def mice. in conclusion, P-sele ctin mediates PMN influx into the peritoneal cavity, while E- and L-se lectins do not appear to play any significant role in the 6 h time per iod following CLP. Lung PMN sequestration, after CLP, occurred indepen dent of P-, E-, or L-selectin expression. Blockade of P-selectin durin g peritonitis appears to be potentially deleterious by preventing earl y PMN influx into the compartment containing the septic focus.